Large proportions of the major reproductive tract inflammatory syndromes remain idiopathic, not attributable to the major sexually transmitted pathogens such as Chlamydia trachomatis or Neisseria gonorrhoeae. Where effective STD control programs exist, most urethritis in men and endocervicitis or mucopurulent cervicitis (MPC) in women is no longer attributable to gonococcal or chlamydial infection. This is equally true for most upper genital tract complications of urethritis (epididymitis) or endocervicitis (endometritis, salpingitis and perinatal and puerperal morbidity). Mycoplasma genitalium, a fastidious bacterium discovered in 1981, now detectable by PCR, has been significantly associated with nongonococcal urethritis (NGU) in men in 11 of 11 studies over the past decade using PCR, including our own recent study which demonstrated M. genitalium in 27 (22%) of 211 men with and 5 (4%) of 117 without NGU (OR 6.5; 95% CI 2.1- 19.9). Recognition of M. genitalium as a pathogen in the male raises the important question of its role as a pathogen in the female, both in nonpregnant and in pregnant women. Since initial submission of this proposal in February 2000, we have completed two retrospective cross- sectional studies involving women. In a random sample of female STD clinic patients, we demonstrated endocervical M. genitalium infection in 24 (13%) of 191 with MPC vs. 27 (6%) of 453 without MPC (OR adjusted for cervical pathogens 3.0; 95% CI 1.6-5.8). This study also detected M. genitalium in 10 (14.3%) of 70 women with history of spontaneous miscarriage at < 20 weeks gestation vs. 41 (7.2%) of 570 without this history (adj OR=2.5; 95% CI 1.1-5.6). A cross-sectional study of 115 Kenyan women with suspected PID demonstrated M. genitalium in endometrial biopsies from 7 (12%) of 58 women with endometritis vs. 0 of 57 without endometritis (p=0.01). In our studies of male urethritis, MPC, and endometritis, associations of M. genitalium with disease were similar to, or stronger than, the associations with chlamydial infection. These data support our proposed studies as the next logical step in clinical epidemiologic studies of this pathogen. Our three specific aims are to (1) define the role of M. genitalium in acute salpingitis in women undergoing laparoscopy in Nairobi Kenya; (2) define the association of M. genitalium with abnormal pregnancy outcomes including preterm delivery of a low birthweight infant, using data and clinical specimens already available from 2500 women prospectively followed to term at University of Washington hospitals (including 625 with gestation <37 weeks); and (3) determine (a) risk factors for M. genitalium infection in a population-based sample of young women participating in Wave 3 of the National Longitudinal Study of Adolescent Health, and in a sample of higher risk women attending the Seattle STD clinic, and (b) concordance of M. genitalium infection in these women and their sex partners. M genitalium may represent an important new pathogen in the female reproductive tract. Studies of its association with salpingitis and pregnancy morbidity are essential. Future studies should also address whether, similar to gonorrhea and chlamydial infection, it facilitates transmission of HIV infection.